Over the past years the Division of Oncology at the Fred Hutchinson Cancer Research Center has been involved in a continuing program of Marrow transplantation for the treatment of patients with advanced, otherwise fatal malignant and non-malignant hemopoietic disease. A number of grafted patients have become long-term survivors without recurrence of their original disease nor with occurrence of graft-versus-host disease. Many patients, however, have died from recurrent disease or, more frequently, from complications related to the transplant. Further improvement of clinical marrow grafting hinges upon progress and better understanding in at least four areas of study: 1) recovery of immunologic reactivity in marrow graft recipients, 2) understanding of mechanisms of stable graft-host tolerance and of graft-versus-host disease, 3) methods of recognizing and overcoming sensitization of a marrow graft recipient by preceding blood transfusions, 4) detection of cell-mediated immunity to leukemia-associated antigens, use of marrow grafting as immunotherapy and study of the association of a non-HLA histocompatibility antigen system and lymphoid malignancy. It is the objective of this proposal to conduct an immunologic investigation in those four areas of study.